Bipolar Depression
Conditions
Brief summary
The study evaluates the efficacy and safety of SM-13496 compared with placebo in patients with Bipolar I Depression.
Detailed description
The primary objective is to compare the efficacy of SM-13496 (20-60 or 80-120 mg/day) monotherapy with that of placebo in patients with depressive symptoms associated with bipolar I disorder by assessing the change from baseline in the MADRS total score at Week 6.
Interventions
DRUGPlacebo
Placebo comparator
DRUGSM-13496
SM-13496 20mg for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6
Sponsors
Sumitomo Pharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Patients who were fully informed of and understand the objectives, procedures, and possible benefits and risks of the study and who provided written voluntary consent to participate in the study. * Outpatients aged 18 through 74 years at the time of consent * Patients meets DSM-IV-TR criteria for bipolar I disorder, most recent episode depressed (≥ 4 weeks and less than 12 months) without psychotic features.
Exclusion criteria
* Patients with imminent risk of suicide or injury to self, others, or property. * Patients who had been hospitalized because of a manic or mixed episode within 60 days prior to screening. * Patients who are otherwise considered ineligible for the study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | Baseline to 6 weeks | Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the SDS Total Score at Week 6 (LOCF) | Baseline to 6 weeks | Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of functional impairment in work/school, social life and family life/home responsibilities. The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items. |
| Change From Baseline in the CGI-BP-S (Depression) Score at Week 6 | Baseline to 6 weeks | Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression. The CGI depression score ranges from a minimum of 1 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. |
| Change From Baseline in the YMRS Total Score at Week 6 | Baseline to 6 weeks | YMRS (Young Mania Rating Scale) is a clinician-rated assessment of the severity of mania in subjects with a diagnosis of bipolar disorder. The YMRS total score ranges from a minimum of 0 to a maximum of 60. For the YMRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The YMRS contains eleven (11) items. The total score is computed as the sum of the scores for the 11 items. |
| Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) | Baseline to 6 weeks | The Hamilton Rating Scale for Anxiety (HAM-A) scale is a rating scale developed to quantify the severity of anxiety symptomatology. The HAM-A total score ranges from a minimum of 0 to a maximum of 56. For the HAM-A total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The HAM-A contains fourteen (14) items. The total score is computed as the sum of the scores for the 14 items. |
Countries
Japan, Lithuania, Malaysia, Philippines, Russia, Slovakia, Taiwan, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo once daily orally
Placebo | 171 |
| SM-13496 20 - 60 mg/Day once daily orally
SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-7 and beginning Day 8 flexibly dosed 20-60 mg/day for Weeks 2-6 | 182 |
| SM-13496 80 - 120 mg/Day once daily orally
SM-13496 (lurasidone HCl): SM-13496 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6, 80 mg/day on Day 7 and beginning Day 8 flexibly dosed 80-120 mg/day for Weeks 2-6 | 169 |
| Total | 522 |
Baseline characteristics
| Characteristic | Total | SM-13496 80 - 120 mg/Day | SM-13496 20 - 60 mg/Day | Placebo |
|---|---|---|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 12.77 | 43.2 years STANDARD_DEVIATION 12.78 | 42.6 years STANDARD_DEVIATION 12.86 | 41.3 years STANDARD_DEVIATION 12.64 |
| Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) | 4.58 units on a scale STANDARD_DEVIATION 0.666 | 4.58 units on a scale STANDARD_DEVIATION 0.603 | 4.57 units on a scale STANDARD_DEVIATION 0.7 | 4.60 units on a scale STANDARD_DEVIATION 0.69 |
| Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score | 30.8 units on a scale STANDARD_DEVIATION 5.35 | 30.8 units on a scale STANDARD_DEVIATION 5.09 | 30.6 units on a scale STANDARD_DEVIATION 5.57 | 30.9 units on a scale STANDARD_DEVIATION 5.39 |
| Race/Ethnicity, Customized Asian | 220 Participants | 66 Participants | 77 Participants | 77 Participants |
| Race/Ethnicity, Customized White | 302 Participants | 103 Participants | 105 Participants | 94 Participants |
| Region of Enrollment Japan | 178 Participants | 53 Participants | 65 Participants | 60 Participants |
| Region of Enrollment Lithuania | 10 Participants | 4 Participants | 4 Participants | 2 Participants |
| Region of Enrollment Malaysia | 19 Participants | 6 Participants | 6 Participants | 7 Participants |
| Region of Enrollment Philippines | 11 Participants | 3 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Russia | 145 Participants | 50 Participants | 51 Participants | 44 Participants |
| Region of Enrollment Slovakia | 16 Participants | 4 Participants | 7 Participants | 5 Participants |
| Region of Enrollment Taiwan | 12 Participants | 4 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Ukraine | 131 Participants | 45 Participants | 43 Participants | 43 Participants |
| Sex: Female, Male Female | 277 Participants | 88 Participants | 95 Participants | 94 Participants |
| Sex: Female, Male Male | 245 Participants | 81 Participants | 87 Participants | 77 Participants |
| Sheehan Disability Scale (SDS) total score | 19.7 units on a scale STANDARD_DEVIATION 5.35 | 19.8 units on a scale STANDARD_DEVIATION 5.58 | 19.4 units on a scale STANDARD_DEVIATION 5.29 | 19.9 units on a scale STANDARD_DEVIATION 5.22 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 172 | 0 / 184 | 0 / 169 |
| other Total, other adverse events | 44 / 172 | 49 / 184 | 75 / 169 |
| serious Total, serious adverse events | 5 / 172 | 2 / 184 | 4 / 169 |
Outcome results
Primary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6
Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items.
Time frame: Baseline to 6 weeks
Population: Intention-to-treat population is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | -10.6 units on a scale | Standard Error 0.72 |
| SM-13496 20 - 60 mg/Day | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | -13.6 units on a scale | Standard Error 0.69 |
| SM-13496 80 - 120 mg/Day | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6 | -12.6 units on a scale | Standard Error 0.73 |
p-value: 0.00795% CI: [-4.9, -1]Mixed Models Analysis
p-value: 0.05795% CI: [-4, 0.1]Mixed Models Analysis
Secondary
Change From Baseline in the CGI-BP-S (Depression) Score at Week 6
Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression. The CGI depression score ranges from a minimum of 1 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.
Time frame: Baseline to 6 weeks
Population: Intention-to-treat population is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the CGI-BP-S (Depression) Score at Week 6 | -1.11 units on a scale | Standard Error 0.092 |
| SM-13496 20 - 60 mg/Day | Change From Baseline in the CGI-BP-S (Depression) Score at Week 6 | -1.51 units on a scale | Standard Error 0.088 |
| SM-13496 80 - 120 mg/Day | Change From Baseline in the CGI-BP-S (Depression) Score at Week 6 | -1.41 units on a scale | Standard Error 0.093 |
p-value: 0.00295% CI: [-0.65, -0.15]Mixed Models Analysis
p-value: 0.01995% CI: [-0.56, -0.05]Mixed Models Analysis
Secondary
Change From Baseline in the HAM-A Total Score at Week 6 (LOCF)
The Hamilton Rating Scale for Anxiety (HAM-A) scale is a rating scale developed to quantify the severity of anxiety symptomatology. The HAM-A total score ranges from a minimum of 0 to a maximum of 56. For the HAM-A total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The HAM-A contains fourteen (14) items. The total score is computed as the sum of the scores for the 14 items.
Time frame: Baseline to 6 weeks
Population: Intention-to-treat population is analyzed. Values were missing for some subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) | -5.7 units on a scale | Standard Error 0.51 |
| SM-13496 20 - 60 mg/Day | Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) | -7.4 units on a scale | Standard Error 0.49 |
| SM-13496 80 - 120 mg/Day | Change From Baseline in the HAM-A Total Score at Week 6 (LOCF) | -6.4 units on a scale | Standard Error 0.5 |
p-value: 0.01695% CI: [-3.1, -0.3]ANCOVA
p-value: 0.29495% CI: [-2.1, 0.7]ANCOVA
Secondary
Change From Baseline in the SDS Total Score at Week 6 (LOCF)
Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of functional impairment in work/school, social life and family life/home responsibilities. The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items.
Time frame: Baseline to 6 weeks
Population: Intention-to-Treat Population is analyzed. Values were missing for some subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the SDS Total Score at Week 6 (LOCF) | -5.7 units on a scale | Standard Error 0.66 |
| SM-13496 20 - 60 mg/Day | Change From Baseline in the SDS Total Score at Week 6 (LOCF) | -7.6 units on a scale | Standard Error 0.62 |
| SM-13496 80 - 120 mg/Day | Change From Baseline in the SDS Total Score at Week 6 (LOCF) | -6.8 units on a scale | Standard Error 0.67 |
p-value: 0.03795% CI: [-3.6, -0.1]ANCOVA
p-value: 0.22395% CI: [-2.9, 0.7]ANCOVA
Secondary
Change From Baseline in the YMRS Total Score at Week 6
YMRS (Young Mania Rating Scale) is a clinician-rated assessment of the severity of mania in subjects with a diagnosis of bipolar disorder. The YMRS total score ranges from a minimum of 0 to a maximum of 60. For the YMRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The YMRS contains eleven (11) items. The total score is computed as the sum of the scores for the 11 items.
Time frame: Baseline to 6 weeks
Population: Intention-to-Treat Population is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the YMRS Total Score at Week 6 | -0.51 units on a scale | Standard Error 0.19 |
| SM-13496 20 - 60 mg/Day | Change From Baseline in the YMRS Total Score at Week 6 | -0.98 units on a scale | Standard Error 0.18 |
| SM-13496 80 - 120 mg/Day | Change From Baseline in the YMRS Total Score at Week 6 | -0.99 units on a scale | Standard Error 0.191 |
p-value: 0.07695% CI: [-0.98, 0.05]Mixed Models Analysis
p-value: 0.07595% CI: [-1.01, 0.05]Mixed Models Analysis